The novel contribution of our study is finding that COL4A5 deficiency may lead to HAS2 overexpression and HA accumulation to activate CD44-TGFβ signaling, thereby promoting fibrosis, possibly suggesting that HAS2 and CD44 are potential therapeutic targets for impeding renal fibrosis in XLAS. Here, TGFB1 is linked to X-linked hydrocephalus with stenosis of the aqueduct of Sylvius.